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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1975 Jun;72(6):2017–2021. doi: 10.1073/pnas.72.6.2017

Method for predicting RNA secondary structure.

J M Pipas, J E McMahon
PMCID: PMC432683  PMID: 1056009

Abstract

We report a method for predicting the most stable secondary structure of RNA from its primary sequence of nucleotides. The technique consists of a series of three computer programs interfaced to take the nucleotide sequence of any RNA and (a) list all possible helical regions, using modified Watson-Crick base-pairing rules; (b) create all possible secondary structures by forming permutations of compatible helical regions; and (c)evaluate each structure for total free energy of formation from a completely extended chain. A free energy distribution and the base-by-base bonding interactions of each possible structure are catalogued by the system and are readily available for examination. The method has been applied to 62 tRNA sequences. The total free-energy of the predicted most stable structures ranged from -19 to -41 kcal/mole (-22 to -49 kJ/mole). The number of structures created was also highly sequence-dependent and ranged from 200 to 13,000. In nearly all cases the cloverleaf is predicted to be the structure with the lowest free energy of formation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cole P. E., Yang S. K., Crothers D. M. Conformational changes of transfer ribonucleic acid. Equilibrium phase diagrams. Biochemistry. 1972 Nov 7;11(23):4358–4368. doi: 10.1021/bi00773a024. [DOI] [PubMed] [Google Scholar]
  2. Crothers D. M., Cole P. E., Hilbers C. W., Shulman R. G. The molecular mechanism of thermal unfolding of Escherichia coli formylmethionine transfer RNA. J Mol Biol. 1974 Jul 25;87(1):63–88. doi: 10.1016/0022-2836(74)90560-9. [DOI] [PubMed] [Google Scholar]
  3. Delisi C., Crothers D. M. Prediction of RNA secondary structure. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2682–2685. doi: 10.1073/pnas.68.11.2682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FRESCO J. R., ALBERTS B. M., DOTY P. Some molecular details of the secondary structure of ribonucleic acid. Nature. 1960 Oct 8;188:98–101. doi: 10.1038/188098a0. [DOI] [PubMed] [Google Scholar]
  5. Fresco J. R., Adams A., Ascione R., Henley D., Lindahl T. Tertiary structure in transfer ribonucleic acids. Cold Spring Harb Symp Quant Biol. 1966;31:527–537. doi: 10.1101/sqb.1966.031.01.068. [DOI] [PubMed] [Google Scholar]
  6. Gartland W. J., Sueoka N. Two interconvertible forms of tryptophanyl sRNA in E. coli. Proc Natl Acad Sci U S A. 1966 Apr;55(4):948–956. doi: 10.1073/pnas.55.4.948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldberger R. F. Autogenous regulation of gene expression. Science. 1974 Mar 1;183(4127):810–816. doi: 10.1126/science.183.4127.810. [DOI] [PubMed] [Google Scholar]
  8. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. 3. Small internal loops resulting from mismatches. J Mol Biol. 1973 Aug 5;78(2):301–319. doi: 10.1016/0022-2836(73)90118-6. [DOI] [PubMed] [Google Scholar]
  9. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. II. Small hairpin loops. J Mol Biol. 1973 Feb 5;73(4):497–511. doi: 10.1016/0022-2836(73)90096-x. [DOI] [PubMed] [Google Scholar]
  10. Gralla J., Steitz J. A., Crothers D. M. Direct physical evidence for secondary structure in an isolated fragment of R17 bacteriophage mRNA. Nature. 1974 Mar 15;248(445):204–208. doi: 10.1038/248204a0. [DOI] [PubMed] [Google Scholar]
  11. Kearns D. R., Wong Y. P., Chang S. H., Hawkins E. Investigation of the structure of native and denatured conformations of tRNALeu3 by high-resolution nuclear magnetic resonance. Biochemistry. 1974 Nov 5;13(23):4736–4746. doi: 10.1021/bi00720a009. [DOI] [PubMed] [Google Scholar]
  12. Kearns D. R., Wong Y. P. Investigation of the secondary structure of Escherichia coli 5 S RNA by high-resolution nuclear magnetic resonance. J Mol Biol. 1974 Aug 25;87(4):755–774. doi: 10.1016/0022-2836(74)90083-7. [DOI] [PubMed] [Google Scholar]
  13. Kim S. H., Suddath F. L., Quigley G. J., McPherson A., Sussman J. L., Wang A. H., Seeman N. C., Rich A. Three-dimensional tertiary structure of yeast phenylalanine transfer RNA. Science. 1974 Aug 2;185(4149):435–440. doi: 10.1126/science.185.4149.435. [DOI] [PubMed] [Google Scholar]
  14. Pace N. R. Structure and synthesis of the ribosomal ribonucleic acid of prokaryotes. Bacteriol Rev. 1973 Dec;37(4):562–603. doi: 10.1128/br.37.4.562-603.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Robertus J. D., Ladner J. E., Finch J. T., Rhodes D., Brown R. S., Clark B. F., Klug A. Structure of yeast phenylalanine tRNA at 3 A resolution. Nature. 1974 Aug 16;250(467):546–551. doi: 10.1038/250546a0. [DOI] [PubMed] [Google Scholar]
  16. Shulman R. G., Hilbers C. W., Wong Y. P., Wong K. L., Lightfoot D. R., Reid B. R., Kearns D. R. Determination of secondary and tertiary structural features of transfer RNA molecules in solution by nuclear magnetic resonance. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2042–2045. doi: 10.1073/pnas.70.7.2042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tinoco I., Jr, Uhlenbeck O. C., Levine M. D. Estimation of secondary structure in ribonucleic acids. Nature. 1971 Apr 9;230(5293):362–367. doi: 10.1038/230362a0. [DOI] [PubMed] [Google Scholar]
  18. Tumanian V. G., Sotnikova L. E., Kholopov A. V. Ob opredelenii vtorichnoi struktury RNK po posledovatel'nosti nukleotidov. Dokl Akad Nauk SSSR. 1966 Feb 21;166(6):1465–1468. [PubMed] [Google Scholar]
  19. Uhlenbeck O. C., Borer P. N., Dengler B., Tinoco I., Jr Stability of RNA hairpin loops: A 6 -C m -U 6 . J Mol Biol. 1973 Feb 5;73(4):483–496. doi: 10.1016/0022-2836(73)90095-8. [DOI] [PubMed] [Google Scholar]
  20. Weissmann C., Billeter M. A., Goodman H. M., Hindley J., Weber H. Structure and function of phage RNA. Annu Rev Biochem. 1973;42:303–328. doi: 10.1146/annurev.bi.42.070173.001511. [DOI] [PubMed] [Google Scholar]

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